Head and Neck Paragangliomas-A Genetic Overview.

Anna Majewska,Małgorzata Wierzbicka,Katarzyna Ziemnicka,Marek Ruchała,Bartłomiej Budny

doi:10.3390/ijms21207669

Anna Majewska, Małgorzata Wierzbicka + Show 3 more

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https://doi.org/10.3390/ijms21207669

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Abstract

Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors. Head and neck paragangliomas (HNPGL) can be categorized into carotid body tumors, which are the most common, as well as jugular, tympanic, and vagal paraganglioma. A review of the current literature was conducted to consolidate knowledge concerning PGL mutations, familial occurrence, and the practical application of this information. Available scientific databases were searched using the keywords head and neck paraganglioma and genetics, and 274 articles in PubMed and 1183 in ScienceDirect were found. From these articles, those concerning genetic changes in HNPGLs were selected. The aim of this review is to describe the known genetic changes and their practical applications. We found that the etiology of the tumors in question is based on genetic changes in the form of either germinal or somatic mutations. 40% of PCC and PGL have a predisposing germline mutation (including VHL, SDHB, SDHD, RET, NF1, THEM127, MAX, SDHC, SDHA, SDHAF2, HIF2A, HRAS, KIF1B, PHD2, and FH). Approximately 25–30% of cases are due to somatic mutations, such as RET, VHL, NF1, MAX, and HIF2A. The tumors were divided into three main clusters by the Cancer Genome Atlas (TCGA); namely, the pseudohypoxia group, the Wnt signaling group, and the kinase signaling group. The review also discusses genetic syndromes, epigenetic changes, and new testing technologies such as next-generation sequencing (NGS).

Highlights

Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors originating from either adrenomedullary chromaffin cells (PCCs); sympathetic ganglia of the thorax (T-PGL); or abdominal (A-PGL), pelvic, or parasympathetic ganglia in the head and neck (HNPGL) [1,2]
The outcomes are presented in the form of a literature review, structured by thematic subsections concerning the classification of head and neck paragangliomas with regard to genetic and molecular changes, as well as elucidation of genetic syndromes
The review presents new methods as they pertain to the investigation of these tumors, such as investigation of epigenetic patterns or the application of new advanced molecular tools like next-generation sequencing (NGS)

Summary

Introduction

Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors originating from either adrenomedullary chromaffin cells (PCCs); sympathetic ganglia of the thorax (T-PGL); or abdominal (A-PGL), pelvic, or parasympathetic ganglia in the head and neck (HNPGL) [1,2]. They are referred to collectively as PPGL. PCC represent 80% to 85% of chromaffin-cell tumors, and PGL represent 15% to 20% [6] These tumors are characteristically well-vascularized and typically benign; roughly 10–15% may metastasize to the lungs, bone, liver, and lymph nodes. Pulsatile tinnitus and conductive hearing loss are characteristic of tympanic paraganglioma [12]

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